Laboratory Investigation

Kidney International (1986) 30, 488–496; doi:10.1038/ki.1986.212

Tubulo-interstitial lesions mediate renal damage in adriamycin glomerulopathy

Tullio Bertani, Franca Cutillo, Carla Zoja, Massimo Broggini and Giuseppe Remuzzi

Mario Negri Institute for Pharmacological Research, Via Gavazzeni 11, 24100 Bergamo, Italy, and Mario Negri Institute for Pharmacological Research, Via Eritrea 62, 20157 Milano, Italy

Correspondence: Dr Giuseppe Remuzzi, Mario Negri Institute for Pharmacological Research, Via Gavazzeni, 11, 24100 Bergamo, Italy.

Received 12 March 1985; Revised 5 August 1985; Re-revised 11 February 1986.

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Abstract

Tubulo-interstitial lesions mediate renal damage in adriamycin glomerulopathy. The present study was designed to investigate the relationship between proteinuria, focal sclerosis, and tubulo-interstitial changes in the evolution of renal damage in experimental nephrosis. We utilized an accelerated unilateral model of adriamycin (ADR) nephrosis characterized by morphological changes more severe than in the classical model. The first events in ADR-induced glomerulopathy were epithelial cell damage and proteinuria. Subsequently, tubular casts were formed at the distal level. The cast formation preceded the development of interstitial damage, which was determined by tubular obstruction and breaking of tubular basement membrane (TBM), which in turn promoted an interstitial inflammatory reaction. Despite the severity of tubulo-interstitial damage observed after a long period of heavy proteinuria, the incidence of focal segmental glomerulosclerosis (FSG) was very low. The results of the present study indicate that chronic proteinuria is not necessarily accompanied by the development of focal sclerosis Tubulo-interstitial lesions appear to be the most important determinant for the progression of renal damage in this model.

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